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Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors.

Publication ,  Journal Article
McNeeley, KM; Karathanasis, E; Annapragada, AV; Bellamkonda, RV
Published in: Biomaterials
August 2009

Long-circulating nanocarriers have been extensively studied to deliver chemotherapeutics; however, the inclusion of targeting agents compromises circulation times thereby offsetting the benefits of active targeting. Here, we formulated cysteine-cleavable phospholipid-polyethylene glycol (PEG) to 'mask' nanocarrier bound targeting ligands from RES clearance and prolong circulation times of liposomes to allow passive targeting to tumors. This detachable polymer coating can be removed after nanocarrier extravasation to tumor is achieved to expose targeting ligands and promote active targeting to tumor cells. In vivo studies on folate receptor-targeted liposomes demonstrated our ability to prolong circulation in the bloodstream using this system thereby verifying the 'masking' capacity of cleavable phospholipid-PEG(5000). Controlled modulation of uptake and cytotoxicity of targeted nanocarriers using cleavable phospholipid-PEG was demonstrated through in vitro studies. Finally, studies analyzing uptake by tumor cells in vivo confirmed enhanced intracellular delivery when tumor-inoculated animals received targeted liposomes containing cleavable phospholipid-PEG(5000) followed by a cysteine infusion to expose folate after liposomes had extravasated to tumor. These results indicate that cleavable phospholipid-PEG can be used in nanocarrier formulations for controlled exposure of targeting ligands to ensure that circulation times remain uncompromised by the inclusion of targeting agents while enabling active targeting to tumors after removal of the polymer coating.

Duke Scholars

Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

August 2009

Volume

30

Issue

23-24

Start / End Page

3986 / 3995

Related Subject Headings

  • Rats
  • Polyethylene Glycols
  • Phospholipids
  • Nanoparticles
  • Liposomes
  • Glioma
  • Flow Cytometry
  • Drug Delivery Systems
  • Cell Line, Tumor
  • Cell Line
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McNeeley, K. M., Karathanasis, E., Annapragada, A. V., & Bellamkonda, R. V. (2009). Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors. Biomaterials, 30(23–24), 3986–3995. https://doi.org/10.1016/j.biomaterials.2009.04.012
McNeeley, Kathleen M., Efstathios Karathanasis, Ananth V. Annapragada, and Ravi V. Bellamkonda. “Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors.Biomaterials 30, no. 23–24 (August 2009): 3986–95. https://doi.org/10.1016/j.biomaterials.2009.04.012.
McNeeley KM, Karathanasis E, Annapragada AV, Bellamkonda RV. Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors. Biomaterials. 2009 Aug;30(23–24):3986–95.
McNeeley, Kathleen M., et al. “Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors.Biomaterials, vol. 30, no. 23–24, Aug. 2009, pp. 3986–95. Epmc, doi:10.1016/j.biomaterials.2009.04.012.
McNeeley KM, Karathanasis E, Annapragada AV, Bellamkonda RV. Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors. Biomaterials. 2009 Aug;30(23–24):3986–3995.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

August 2009

Volume

30

Issue

23-24

Start / End Page

3986 / 3995

Related Subject Headings

  • Rats
  • Polyethylene Glycols
  • Phospholipids
  • Nanoparticles
  • Liposomes
  • Glioma
  • Flow Cytometry
  • Drug Delivery Systems
  • Cell Line, Tumor
  • Cell Line